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Cited by 52Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchAdvanced Proteomics Techniques and Applications

Large‐scale deep proteomic analysis in Alzheimer's disease brain regions across race and ethnicity

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Seifar, Fatemeh, Fox, Edward J., Shantaraman, Anantharaman, Liu, Yue, Dammer, Eric B., Modeste, Erica, Duong, Duc M., Yin, Luming +42 more·2024·Alzheimer's & Dementia
DOI 10.1002/alz.14360PMC PMC11667503

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Abstract

INTRODUCTION: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within non‐Hispanic White (NHW) populations. Here we provide an extensive survey of the proteomic landscape of AD across diverse racial/ethnic groups. METHODS: Two cortical regions, from multiple centers, were harmonized by uniform neuropathological diagnosis. Among 998 unique donors, 273 donors self‐identified as African American, 229 as Latino American, and 434 as NHW. RESULTS: While amyloid precursor protein and the microtubule‐associated protein tau demonstrated higher abundance in AD brains, no significant race‐related differences were observed. Further proteome‐wide and focused analyses (specific amyloid beta [Aβ] species and the tau domains) supported the absence of racial differences in these AD pathologies within the brain proteome. DISCUSSION: Our findings indicate that the racial differences in AD risk and clinical presentation are not underpinned by dramatically divergent patterns in the brain proteome, suggesting that other determinants account for these clinical disparities. Highlights: We present a large‐scale proteome (∼10,000 proteins) of DLPFC (998) and STG (244) across AD cases. About 50% of samples were from racially and ethnically diverse brain donors. Key AD proteins (amyloid and tau) correlated with CERAD and Braak stages. No significant race‐related differences in amyloid and tau protein levels were observed in AD brains. AD‐associated protein changes showed a strong correlation between the brain proteomes of African American and White individuals. This dataset advances understanding of ethnoracial‐specific AD pathways and potential therapies.

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  • 58% of the significant proteins in AD dementia identified here overlapped with a recent large-scale proteomics study and showed concordant directions of association.

    “When compared with a recent large‐scale proteomics study across diverse racial and ethnic groups, 83 58% of the significant proteins in AD dementia and 68% of the significant proteins in amyloid identified here overlapped with their findings and showed concordant directions of association.”

    From Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes (2025) · cites this paper as [83]

  • 68% of the significant proteins in amyloid identified here overlapped with a recent large-scale proteomics study and showed concordant directions of association.

    “When compared with a recent large‐scale proteomics study across diverse racial and ethnic groups, 83 58% of the significant proteins in AD dementia and 68% of the significant proteins in amyloid identified here overlapped with their findings and showed concordant directions of association.”

    From Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes (2025) · cites this paper as [83]

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Authors
Seifar, F., Fox, E. J., Shantaraman, A., Liu, Y., Dammer, E. B., Modeste, E., Duong, D. M., Yin, L., Trautwig, A. N., Guo, Q., Xu, K., Ping, L., Reddy, J. S., Allen, M., Quicksall, Z., Heath, L., Scanlan, J., Wang, E., Wang, M., Linden, A. V., Poehlman, W., Chen, X., Baheti, S., Ho, C., Nguyen, T., Yepez, G., Mitchell, A. O., Oatman, S. R., Wang, X., Carrasquillo, M. M., Runnels, A., Beach, T., Serrano, G. E., Dickson, D. W., Lee, E. B., Golde, T. E., Prokop, S., Barnes, L. L., Zhang, B., Haroutunian, V., Gearing, M., Lah, J. J., De Jager, P., Bennett, D. A., Greenwood, A., Ertekin‐Taner, N., Levey, A. I., Wingo, A., Wingo, T., & Seyfried, N. T.
Affiliations
  • Emory University (US)
  • Mayo Clinic in Florida (US)
  • Sage Bionetworks (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • New York Genome Center (US)
  • Banner Sun Health Research Institute (US)
  • University of Pennsylvania (US)
  • University of Florida (US)
  • Rush University Medical Center (US)
  • Columbia University Irving Medical Center New York New York USA
Corresponding author
Seyfried, Nicholas T.
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2024-11-13
Volume
20
Issue
12
Pages
8878-8897
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1002/alz.14360
PMC
PMC11667503
OpenAlex
W4404326068
Cited by
52
References
20
Citations by year
2026: 19 · 2025: 30 · 2024: 3
FWCI
14.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s & Dementia (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
Funders
National Institute on Aging (U01‐AG061357)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
Alzheimer's disease, brain proteome

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